- Clinical data released Friday provide more evidence that an immune system-regulating drug from Pfizer works, but it is unclear whether efficacy will be shadowed by broader concerns about safety of the class.
- The late-stage trial found patients with moderate to severe eczema who took Pfizer's abrocitinib had significantly clearer skin and less severe eczema than those on placebo. The readout comes a few months after the drug succeeded in another pivotal study of eczema patients.
- Abrocitinib is part of a drug class that inhibits cell-signaling enzymes called Janus kinases, or JAKs. While effective, the class has raised concerns about increased risks of blood clots and cardiovascular events. Friday's readout found 1.3% of patients on placebo experienced a serious side effect, compared to 3.2% and 1.3% in the two abrocitinib arms. Pfizer also reported that one patient with existing cardiovascular risk factors who was taking 100 mg abrocitinib died three weeks after completing treatment. The study investigator deemed the death unrelated to the drug.
Pfizer knows the perks of having a marketed JAK inhibitor. Its drug Xeljanz (tofacitinib), which holds approvals across three immunological diseases, took in $1 billion dollars in 2019 sales by the end of June.
Yet safety continues to challenge the class. Earlier this year, the Food and Drug Administration strapped Xeljanz with a boxed warning for increased risk of blood clots and of death, specifically for the 10 mg twice daily regimen. The decision came after a post-marketing study found death rates were higher among patients on that regimen versus both a lower Xeljanz dose and an anti-TNF therapy.
Eli Lilly's Olumiant (baricitinib), another JAK drug, only received FDA approval at its lower dose, and carries too a boxed warning about blood clots. Regulators put a similar warning on AbbVie's Rinvoq (upadacitinib) despite late-stage data showing lower rates of thrombosis for patients treated with the drug as opposed to placebo.
Analysts expect safety to be a lasting problem for the class, which could negatively impact its market opportunity.
Black box language for JAK inhibitors in rheumatoid arthritis
|Company||Drug||Black box language on thrombosis|
|Pfizer||Xeljanz||"Rheumatoid arthritis patients with at least one cardiovascular (CV) risk factor had a higher rate of all-cause mortality and thrombosis with Xeljanz 10 mg twice daily vs. 5 mg twice daily or TNF blockers."|
|Eli Lilly||Olumiant||"Thrombosis, including deep venous thrombosis, pulmonary
embolism, and arterial thrombosis, some fatal, have occurred
in patients treated with Olumiant. Patients with symptoms
of thrombosis should be evaluated promptly."
|AbbVie||Rinvoq||"Thrombosis, including deep vein thrombosis, pulmonary
embolism, and arterial thrombosis, have occurred in patients
treated with Janus kinase inhibitors used to treat inflammatory
On the safety front, the second pivotal Phase 3 study of abrocitinib in eczema was fairly consistent with the first, according to Pfizer. Treatment-emergent adverse events were observed in 54%, 63%, and 66% of the patients receiving placebo, 100 mg abrocitinib, and 200 mg abrocitinib, respectively.
Discontinuation rates from adverse events were low across the two abrocitinib arms, Pfizer said, with the lower dose at 3.8% and the higher dose at 3.2%. Nearly 13% of the placebo group dropped out from the study because of side effects.
Pfizer intends to present full results from the first Phase 3 pivotal study of abrocitinib in eczema next month, at a scientific meeting in Madrid. Results from the second trial will also be submitted for presentation at a future scientific meeting.